Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

BACH2 is repurposed following Treg lineage commitment to drive the functional quiescence and maintenance of resting Treg cells

ABSTRACT: In various tissues, cellular homeostasis is achieved by functionally quiescent stem cells which self renew while giving rise to differentiated progeny. Regulatory T (Treg) cells are composed of functionally quiescent resting Treg (rTreg) cells which differentiate into activated Treg (aTreg) cells upon antigen stimulation. How rTreg cells remain quiescent despite chronic exposure to cognate self- and foreign antigens is unclear. The transcription factor BACH2 is critical for early Treg lineage specification but its function following lineage commitment is unresolved. Here, we show Bach2 is highly expressed in lineage-committed rTreg cells but is downregulated in aTreg cells, and upon inflammation. BACH2 binds to AP-1 sites within Treg genomes and its high expression within rTreg cells functions to restrain their TCR-driven activation and differentiation into aTreg cells. As a consequence, cell-autonomous BACH2 expression is required following Treg lineage commitment for the functional quiescence and long-term maintenance of Treg cell populations and for immune homeostasis. This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE128176 | GEO | 2020/05/12

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Distribution of genome-wide BACH2 or JunD binding sites identified by ChIP-Seq in iTreg cells

Project description:In various tissues, cellular homeostasis is achieved by functionally quiescent stem cells which selfrenew while giving rise to differentiated progeny. Regulatory T (Treg) cells are composed of functionally quiescent resting Treg (rTreg) cells which differentiate into activated Treg (aTreg) cells upon antigen stimulation. How rTreg cells remain quiescent despite chronic exposure to cognate self- and foreign antigens is unclear. The transcription factor BACH2 is critical for early Treg lineage specification but its function following lineage commitment is unresolved. Here, we show Bach2 is highly expressed in lineage-committed rTreg cells but is downregulated in aTreg cells, and upon inflammation. BACH2 binds to AP-1 sites within Treg genomes and its high expression within rTreg cells functions to restrain their TCR-driven activation and differentiation into aTreg cells. As a consequence, cell-autonomous BACH2 expression is required following Treg lineagecommitment for the functional quiescence and long-term maintenance of Treg cell populations and for immune homeostasis.

2020-05-12 | GSE127695 | GEO

Transcription profiling of human AICD resistent TReg vs. CD4+CD25high TReg cells

Project description:In this screen we compared cDNA from rTreg (AICD resistent TReg cells) against cDNA derived from all CD4+CD25hi Treg for further molecular characterization of rTreg Experiment Overall Design: Single comparison of rTReg vs. TReg. We pooled rTreg-cDNA derived from FACS-sorted CD4+CD25hi Treg of eight healthy blood donors and performed gene chip microarray analysis.

2008-06-12 | E-GEOD-4243 | biostudies-arrayexpress

Heterogeneous Bach2 expression distinguishes rTreg cells and aTreg cells

Project description:Heterogeneous Bach2 expression distinguishes rTreg cells and aTreg cells

| PRJNA527354 | ENA

BACH2 is repurposed following Treg lineage commitment to drive the functional quiescence and maintenance of resting Treg cells

Project description:BACH2 is repurposed following Treg lineage commitment to drive the functional quiescence and maintenance of resting Treg cells

| PRJNA527220 | ENA

Differential expression pattern in AICD resistent TReg vs. CD4+CD25high TReg cells

2006-06-15 | GSE4243 | GEO

Bach2 represses effector programmes to stabilize Treg-mediated immune homeostasis

Project description:Through their functional diversification, CD4+ T cells play key roles in both driving and constraining immune-mediated pathology. Transcription factors are critical in the generation and maintenance of cellular diversity and negative regulators antagonistic to alternate fates often act in conjunction with positive regulators to stabilize lineage specification1. Polymorphisms within the locus encoding a transcription factor BACH2 are associated with diverse immune-mediated diseases including asthma2, multiple sclerosis3, Crohn¹s disease4-5, coeliac disease6, vitiligo7 and type 1 diabetes8. A role for Bach2 in maintaining immune homeostasis, however, has not been established. Here, we define Bach2 as a broad regulator of immune activation that stabilizes immunoregulatory capacity while repressing the differentiation programmes of multiple effector lineages in CD4+ T cells. Bach2 was required for efficient formation of regulatory (Treg) cells and consequently for suppression of lethal inflammation in a manner that was Treg cell dependent. Assessment of the genome-wide function of Bach2, however, revealed that it represses genes associated with effector cell differentiation. Consequently, its absence during Treg polarization resulted in inappropriate diversion to effector lineages. In addition, Bach2 constrained full effector differentiation within Th1, Th2 and Th17 cell lineages. These findings identify Bach2 as a key regulator of CD4+ T-cell differentiation that prevents inflammatory disease by controlling the balance between tolerance and immunity. The role of Bach2t to regulate immune homeostasis was investigated by mapping DNA binding profiles of Bach2 in iTreg condition. The function of Bach2 was also evaluated by comparing transcriptome in WT and Bach2-deficient iTreg cells and further comparison was done with transcriptome in naive, Th1, Th2, and Th17 conditions.

2013-06-27 | E-GEOD-45975 | biostudies-arrayexpress

Bach2 represses effector programmes to stabilize Treg-mediated immune homeostasis

2013-06-27 | GSE45975 | GEO

Gene expression in Bach2-deficient and wildtype CD4 single-positive thymocytes from mixed chimeric animals

Project description:The role of FoxP3+ regulatory T (Treg) cells in the maintenance of immunological tolerance is well established. Recently, genome-wide association studies (GWAS) in humans have associated polymorphisms within the BACH2 locus encoding the transcription factor BTB and CNC homology 1, basic leucine zipper transcription factor 2 (Bach2) with diverse allergic and autoimmune diseases including asthma, multiple sclerosis, Crohn's disease, celiac disease, generalized vitiligo and type 1 diabetes. Common to these diseases is a failure to adequately maintain immunological tolerance. However, a role for Bach2 in this process has not been established. Here, by assessing the phenotype of mice in which the Bach2 gene is disrupted, we demonstrate a non-redundant role for Bach2 in the prevention of a spontaneous lethal inflammatory disorder predominantly affecting the lung and gut with excessive T helper 2 (Th2) responses and formation of circulating autoantibodies. Bach2 was necessary for efficient induction of FoxP3 expression both during thymopoesis and upon stimulation of naïve peripheral CD4+ T cells under Treg polarizing conditions in vitro. Consequently, in bone marrow reconstitution experiments, Bach2 expression within the haematopoetic system was necessary for suppression of lethal autoimmunity in a manner that was FoxP3 dependent. These findings demonstrate a requirement for Bach2 in early lineage commitment of both thymic and induced Treg cells and point to shared mechanisms that underlie diverse allergic and autoimmune disorders that may serve as targets in the development of novel therapeutic strategies. Six samples were collected from separate mice: three Ly5.1+ wildtype thymocyte samples (biological replicates) and three Ly5.1- Bach2 knockout thymocyte samples (biological replicates).

2013-11-01 | E-GEOD-42598 | biostudies-arrayexpress

Novel Foxo1-dependent Transcriptional Programs Control Treg Cell Function [ChIP-Seq]

Project description:Regulatory T (Treg) cells characterized by expression of the transcription factor forkhead box P3 (Foxp3) maintain immune homeostasis by suppressing self-destructive immune responses1-4. Foxp3 operates as a late acting differentiation factor controlling Treg cell homeostasis and function5, whereas the early Treg cell lineage commitment is regulated by the Akt kinase and the forkhead box O (Foxo) family of transcription factors6-10. However, whether Foxo proteins act beyond the Treg cell commitment stage to control Treg cell homeostasis and function remains largely unexplored. Here we show that Foxo1 is a pivotal regulator of Treg cell function. Treg cells express high amounts of Foxo1, and display reduced T-cell receptor-induced Akt activation, Foxo1 phosphorylation, and Foxo1 nuclear exclusion. Mice with Treg cell-specific deletion of Foxo1 develop a fatal inflammatory disorder similar in severity to Foxp3-deficient mice, but without the loss of Treg cells. Genome-wide analysis of Foxo1 binding sites reveals ~300 Foxo1-bound target genes, including the proinflammatory cytokine Ifng, that do not appear to be directly regulated by Foxp3. These findings demonstrate that the evolutionarily ancient Akt-Foxo1 signaling module controls a novel genetic program indispensable for Treg cell function. Treg cells were isolated from wild-type B6 mice or Foxo1tagBirA mice in which foxo1 is endogenously biotinylated. Foxo1 binding targets in Treg cells were identified by using Foxo1 antibody- and Streptavidin- ChIP-Seq approaches.

2012-09-07 | E-GEOD-40656 | biostudies-arrayexpress

Bach2 attenuates IL-2R signalling to control Treg homeostasis and Tfr development

Project description:Differentiation and homeostasis of Foxp3 + regulatory T cells (Tregs) are tightly controlled by the interleukin-2 receptor (IL-2R) signaling, yet the mechanisms governing these processes are incompletely understood. Here we report that transcription factor Bach2 attenuates IL-2R signaling to coordinate Treg differentiation and homeostasis by directly repressed CD25 (IL-2Rα). Thus, Bach2 balances IL-2R signaling to orchestrate development and homeostasis of various Treg subsets.

2021-05-11 | GSE164937 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data